A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Effect of Milling on Slip Casting of Partially Stabilized Zirconia

Specimens of partially stabilized zirconia were slip cast from aqueous suspensions and sintered at 1500°C for 3 h. The relative density of the cast specimens and the firing shrinkage of the sintered specimens depend on the milling time for the suspension. Vickers hardness and K_IC values of 11.46±s0.07 GN/m² and 6.10 ±0.04 MN.m^3/2, respectively, were obtained for all sintered specimens. The dispersion of the suspension is important in increasing the relative density of the cast specimens.     

Applications of computer and numerical analysis techniques in welding research

In recent years, computer technology has made remarkable progress and a computer has become an indispensable tool for both engineers and scientists. In this article, utilization of computers in welding research is briefly summarized. Their use in numerical analysis is particularly discussed and applied to physical phenomena in molten pool, hydrogen diffusion and residual stresses due to welding. A comparison is made between theoretical and experimental results.     

Preoperative thermochemotherapy of oral cancer using magnetic induction hyperthermia (Implant Heating System: IHS)

This study investigated the impact of Difficulty Level and Type of Suggestion upon the durability of posthypnotic suggestion over an 8-week period. Seventy-eight highly susceptible subjects selected by both the Harvard Group Scale of Hypnotic Susceptibility: Form A (HGSHS:A) and Stanford Hypnotic Scale of Susceptibility: Form C (SHSS:C) were assigned to six groups (two levels of Difficulty x three Types of Suggestion). S's were tested for posthypnotic suggestion at 1, 3, 6, and 8 weeks. A 2 x 3 x 4 (Difficulty x Suggestion x Time) factorial ANOVA was conducted, with Time treated as a repeated-measure. The outcome variable at each time was either pass or fail for relevant suggestion. We found a significant Time effect, a significant Difficulty effect, and a significant Time x Difficulty interaction. Fewer subjects passed the difficult suggestions than passed the easy suggestions; fewer passed suggestions at a latter time; and the decay in pass rate was more pronounced for the easy suggestion condition, due largely to the higher initial pass rate. Type of Suggestion was not significant, nor were any of the other interactions. Clinical implications were discussed.     

A CMOS integrated circuit for multichannel multiple-subjectbiotelemetry using bidirectional optical transmissions [weightlessnessin space effects application]

A CMOS integrated circuit for a noninvasive biological-signal telemetry system specified for use in medical and physiological studies of the influence of weightlessness in space is presented. The system can monitor multichannel (4 channels maximum) biological signals from multiple subjects (4 subjects maximum) in real time by using time multiplexing. A key technique so-called synchronized multiple-subject telemetry, to achieve multiple-subject telemetry has been proposed. This technique utilizes bidirectional optical transmissions with direct and scattered infrared lights between an observer and each of the subjects. An experimental CMOS IC to give a small light-weight low-power, and smart telemetry instrument for use on animals has been developed. This IC is for evaluating circuit blocks of the implantable monolithic telemetry instrument. The major circuit blocks include CMOS digital circuits for synchronization, subject selection and time multiplexing, analog circuits for pulse interval modulation, and other blocks such as a CMOS optical pulse receiver and an LED driver. A preliminary experimental multichannel telemetry from two subjects has been performed with the implemented IC chips, and the principal operation of the multiple-subject optical biotelemetry has been demonstrated     

Which vessel is more important in the supercharged flap--artery, vein, or both? An experimental study

The supercharged flap is one which is expected to attain better survival, by anastomosing the distal vessels of the flap to the recipient vessels. An experimental study is reported to determine whether the vessel to be anastomosed should be an artery, a vein, or both. The authors advise anastomosing an artery and a vein, but they believe that arterial inflow is more important than venous drainage.     

Electron transport in InGaO3(ZnO)m (m=integer) studied using single-crystalline thin films and transparent MISFETs

We have investigated the characteristics of transparent metal-insulator-semiconductor field-effect transistors (MISFETs) fabricated using InGaO₃(ZnO)_m (m=integer) single-crystalline thin films as n-channel layers and amorphous alumina as gate insulator films. The MISFETs exhibit good characteristics such as insensitivity to visible light illumination, off-current as low as ∼1 nA with a positive threshold voltage of ∼3 V and on/off current ratio of 10⁵. The field-effect mobility increased from ∼1 to ∼10 cm² (V s)⁻¹ as the m-value increased. Room temperature Hall mobility also increased. However, unexpectedly these values were lower than the field-effect mobility. It is explained by existence of shallow localized state in the homologous compounds.